Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Flavobacterium eburneum sp. nov., isolated from reclaimed saline land soil

Hwang, Woon Mo, Kim, Dohak, Kang, Keunsoo, Ahn, Tae-Young (2017): Flavobacterium eburneum sp. nov., isolated from reclaimed saline land soil. International Journal of Systematic and Evolutionary Microbiology 67 (1): 55-59, DOI: 10.1099/ijsem.0.001568, URL: http://dx.doi.org/10.1099/ijsem.0.00156

Electrostatic shock acceleration of ions in near-critical-density plasma driven by a femtosecond petawatt laser

© 2020, The Author(s). With the recent advances in ultrahigh intensity lasers, exotic astrophysical phenomena can be investigated in laboratory environments. Collisionless shock in a plasma, prevalent in astrophysical events, is produced when a strong electric or electromagnetic force induces a shock structure in a time scale shorter than the collision time of charged particles. A near-critical-density (NCD) plasma, generated with an intense femtosecond laser, can be utilized to excite a collisionless shock due to its efficient and rapid energy absorption. We present electrostatic shock acceleration (ESA) in experiments performed with a high-density helium gas jet, containing a small fraction of hydrogen, irradiated with a 30 fs, petawatt laser. The onset of ESA exhibited a strong dependence on plasma density, consistent with the result of particle-in-cell simulations on relativistic plasma dynamics. The mass-dependent ESA in the NCD plasma, confirmed by the preferential reflection of only protons with two times the shock velocity, opens a new possibility of selective acceleration of ions by electrostatic shock11sciescopu